de procédés propres et compacts utilisant le CO2 supercritique :
Génération de particules
Publications scientifiques au M2P2
Elisabeth Badens, Yasmine Masmoudi, Adil Mouahid, Christelle Crampon. Current situation and perspectives in drug formulation by using supercritical fluid technology. Journal of Supercritical Fluids, Elsevier, 2018, 134, pp.274 - 283. 〈10.1016/j.supflu.2017.12.038〉. 〈hal-01815987〉 Plus de détails...
Supercritical fluid (SCF) technology has been applied to drug product development over the last thirty years and drug particle generation using SCFs appears to be an efficient way to carry out drug formulation which will form end-products meeting targeted specifications. This article presents an overview of drug particle design using SCFs from a rather different perspective than usual, more focused on chemical and process engineering aspects. The main types of existing processes are described in a concise way and a focus is put on how to choose the right operating conditions considering both thermodynamic and hydrodynamic aspects. It is shown that the operating conditions and parameters can be easily optimized so as to facilitate the further process scale-up. Furthermore, the new trends in particle generation using SCFs are introduced, related either to new types of drug medicines that are treated or new ways of process implementation methods.
Elisabeth Badens, Yasmine Masmoudi, Adil Mouahid, Christelle Crampon. Current situation and perspectives in drug formulation by using supercritical fluid technology. Journal of Supercritical Fluids, Elsevier, 2018, 134, pp.274 - 283. 〈10.1016/j.supflu.2017.12.038〉. 〈hal-01815987〉
Abir Bouledjouidja, Yasmine Masmoudi, M. Sergent, Elisabeth Badens. Effect of operational conditions on the supercritical carbon dioxide impregnation of anti-inflammatory and antibiotic drugs in rigid commercial intraocular lenses. Journal of Supercritical Fluids, Elsevier, 2017, 130, pp.63 - 75. 〈http://dx.doi.org/10.1016/j.supflu.2017.07.015〉. 〈10.1016/j.supflu.2017.07.015〉. 〈hal-01578745〉 Plus de détails...
Drug/lense combinations have proven significant in the field of ocular therapeutics. The development of innovative systems and elaboration processes is an upcoming issue for ocular drug delivery. One challenging issue is the elaboration of drug loaded intraocular lenses (IOLs) to combine cataract surgery and post-operative treatments in a single procedure. In this work, we are studying the elaboration of such systems while using a green process using supercritical fluids for impregnating ophthalmic drugs on commercial IOLs. More particularly, rigid commercial intraocular lenses made from Poly (Methyl MethAcrylate) (PMMA), used in cataract surgery, are loaded with dexamethasone 21- phosphate disodium salt (DXP, an anti-inflammatory drug) and ciprofloxacin (CIP, an antibiotic) in order to prevent short- and mid-term postoperative complications. Supercritical impregnations were carried out in a batch mode and impregnation yields were determined through drug release kinetic studies in a solution simulating the aqueous humor. Before performing an experimental design, preliminary impregnation assays were conducted in order to delimit the operating domain. Transparent IOLs presenting an effective impregnation were obtained. The highest impregnation yields for DXP and CIP in PMMA IOLs were 18.3 and 2.8 μgdrug/mgIOL respectively. Despite the low solubility of each drug in the fluid phase, homogeneous and in-depth impregnations were successfully obtained with a prolonged drug delivery (about 40 days) for most impregnation experiments.
Abir Bouledjouidja, Yasmine Masmoudi, M. Sergent, Elisabeth Badens. Effect of operational conditions on the supercritical carbon dioxide impregnation of anti-inflammatory and antibiotic drugs in rigid commercial intraocular lenses. Journal of Supercritical Fluids, Elsevier, 2017, 130, pp.63 - 75. 〈http://dx.doi.org/10.1016/j.supflu.2017.07.015〉. 〈10.1016/j.supflu.2017.07.015〉. 〈hal-01578745〉
Rania Djerafi, Andri Swanepoel, Christelle Crampon, Lonji Kalombo, Philip Labuschagne, et al.. Supercritical antisolvent co-precipitation of rifampicin and ethyl cellulose. European Journal of Pharmaceutical Sciences, Elsevier, 2017, 102, pp.161 - 171. 〈http://www.sciencedirect.com/science/article/pii/S0928098717301495〉. 〈10.1016/j.ejps.2017.03.016〉. 〈hal-01524709〉 Plus de détails...
Abir Bouledjouidja, Yasmine Masmoudi, Michiel Van Speybroeck, Laurent Schueller, Elisabeth Badens. Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide. International Journal of Pharmaceutics, Elsevier, 2016, 499, pp.1 - 9. 〈hal-01266561〉 Plus de détails...
Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drug's dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug. While incipient wetness method led to a Fenofibrate loading up to 300 mgdrug/gsilica in 48 h of impregnation, the supercritical impregnation method yielded loading up to 485 mgdrug/gsilica in 120 min of impregnation duration, at 16 MPa and 308 K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation.
Abir Bouledjouidja, Yasmine Masmoudi, Michiel Van Speybroeck, Laurent Schueller, Elisabeth Badens. Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide. International Journal of Pharmaceutics, Elsevier, 2016, 499, pp.1 - 9. 〈hal-01266561〉
Abir Bouledjouidja, Yasmine Masmoudi, Michelle Sergent, Vivek Trivedi, Abdeslam-Hassen Meniai, et al.. Drug loading of foldable commercial intraocular lenses using supercritical impregnation
. International Journal of Pharmaceutics, Elsevier, 2016, 500, pp.85 - 99. 〈hal-01266557〉 Plus de détails...
The drug delivery through intraocular lenses (IOLs) allows the combination of cataract surgery act and postoperative treatment in a single procedure. In order to prepare such systems, “clean” supercritical CO2 processes are studied for loading commercial IOLs with ophthalmic drugs. Ciprofloxacin (CIP, an antibiotic) and dexamethasone 21-phosphate disodium (DXP, an anti-inflammatory drug) were impregnated into foldable IOLs made from poly-2-hydroxyethyl methacrylate (P-HEMA). A first pre-treatment step was conducted in order to remove absorbed conditioning physiological solution. Supercritical impregnations were then performed by varying the experimental conditions. In order to obtain transparent IOLs and avoid the appearance of undesirable foaming, it was necessary to couple slow pressurization and depressurization phases during supercritical treatments. The impregnation yields were determined through drug release studies. For both drugs, release studies showdeep and reproducible impregnation for different diopters. For the system P-HEMA/CIP, a series of impregnations was performed to delimit the experimental range at two pressures (80 and 200 bar) in the presence or absence of ethanol as a co-solvent for two diopters (+5.0 D and +21.0 D). Increase in pressure in the absence of a co-solvent resulted in improved CIP impregnation. The addition of ethanol (5 mol%) produced impregnation yields comparable to those obtained at 200 bar without co-solvent. A response surface methodology based on experimental designs was used to study the influence of operating conditions on impregnation of IOLs (+21.0 D) in the absence of co-solvent. Two input variables with 5 levels each were considered; the pressure (80–200 bar) and the impregnation duration (30–240 min). CIP impregnation yields ranging between 0.92 and 3.83 μgCIP/mgIOL were obtained from these experiments and response surface indicated the pressure as a key factor in the process. The DXP impregnation in P-HEMA was higher than CIP at all the tested conditions (8.50–14.53 μgDXP/mgIOL). Furthermore, unlike CIP, highest DXP impregnation yields were obtained in the presence of ethanol as a co-solvent (5 mol%). NMR spectroscopy was performed to confirm complete removal of ethanol in the co-solvent-treated IOLs
Abir Bouledjouidja, Yasmine Masmoudi, Michelle Sergent, Vivek Trivedi, Abdeslam-Hassen Meniai, et al.. Drug loading of foldable commercial intraocular lenses using supercritical impregnation
. International Journal of Pharmaceutics, Elsevier, 2016, 500, pp.85 - 99. 〈hal-01266557〉
L.M. Santiago, Y. Masmoudi, A. Tarancón, R. Djerafi, H. Bagán, et al.. Polystyrene based sub-micron scintillating particles produced by supercritical anti-solvent precipitation. Journal of Supercritical Fluids, Elsevier, 2015, 103, pp.18-27. 〈10.1016/j.supflu.2015.04.015〉. 〈hal-01297575〉 Plus de détails...
scintillation microspheres (PSm) are a novel material employed in the measurement of radioactivity (α and β emitters). This work is focused on the formation of plastic scintillation particles through the precipitation and encapsulation of two fluorescent solutes (2,5-diphenyloxazol (PPO) and 1,4-Bis(5-phenyloxazol-2-yl) benzene (POPOP)) and an aromatic solvent 2,6-diisopropyl-naphthalene (DIN), which acts as an enhancer for α and β emitters discrimination, into a polymeric matrix of Polystyrene (PS) by Supercritical Anti-Solvent process (SAS) using ethyl acetate (EtAc) for dissolving the PS and supercritical CO2 as antisolvent. Different process parameters were varied; solute concentration in the organic solution (W, wt%), injection velocity of the organic solution (u, ms−1), molar ratio of the organic solvent regarding to CO2 (XEA) and injection capillary tube diameter (μm). In the different experimental conditions tested, SAS coprecipitation was successfully achieved resulting in yields higher than 90% and very low quantities of residual solvent (600–1200 ppm). The different Polystyrene based particles obtained were nearly spherical sub-micron particles (ranged between 150 and 400 nm) and also agglomerates of a few micrometers were observed in most of the studied conditions. Radiometric capacities of particles were evaluated through measuring different beta and alpha emitting radionuclide. The coprecipitates showed scintillation behavior when fluorescent solutes were added, therefore confirming their encapsulation.
L.M. Santiago, Y. Masmoudi, A. Tarancón, R. Djerafi, H. Bagán, et al.. Polystyrene based sub-micron scintillating particles produced by supercritical anti-solvent precipitation. Journal of Supercritical Fluids, Elsevier, 2015, 103, pp.18-27. 〈10.1016/j.supflu.2015.04.015〉. 〈hal-01297575〉
Quercetin is a strong naturally occurring antioxidant that is exploited in pharmaceutical and cosmeticsapplications. Unfortunately, quercetin is highly susceptible to oxidation. Besides, its poor solubility inwater and low bioavailability upon oral administration limit the use in drug formulations for the treat-ment of human diseases. In an effort to overcome these drawbacks, the micronization and coprecipitationof quercetin particles with a low-cost biocompatible polymer (ethyl cellulose, EC) was studied by usingsupercritical anti-solvent process (SAS) with a non-toxic solvent ethyl acetate. The results showed thatSAS micronization of quercetin led to a reduction in the quercetin particle size and crystallinity withouta change in the needle-like habit. SAS coprecipitation of quercetin with EC at moderate pressure andtemperature (10 MPa and 35◦C) led to obtaining quasi-spherical particles. The coated polymer avoidthe growth of quercetin crystals, thus amorphous particles in the submicron range (mean size rangingbetween 150 and 350 nm) were formed. Promising coprecipitation results were reached with quite highprocess yields (above 85%) and encapsulation efficiencies up to 99% that provided a high stability to thecoated quercetin with EC against oxidation.
Maria Teresa Fernández-Ponce, Yasmine Masmoudi, Rania Djerafi, Lourdes Casas, Casimiro Mantell, et al.. Particle design applied to quercetin using supercritical anti-solvent techniques. Journal of Supercritical Fluids, Elsevier, 2015, 105, pp.119 - 127. 〈hal-01266553〉
Luz-M. Santiago, Yasmine Masmoudi, Alex Tarancón, Rania Djerafi, Héctor Bagán, et al.. Polystyrene based sub-micron scintillating particles produced bysupercritical anti-solvent precipitation. Journal of Supercritical Fluids, Elsevier, 2015, 103, pp.18 - 27. 〈hal-01266416〉 Plus de détails...
Supercritical anti-solvent (SAS) process is considered to be a clean technology suitable for particle design. It is generally used in order to micronize compounds of interest under mild operating conditions of temperature and with very low residual solvent traces in the end-product. By varying the process parameters, the properties of the produced powders can be adjusted with defined size (generally micron or nanometer sized particles), morphology and a narrow particle size distribution. There is currently a growing interest for the elaboration of controlled delivery systems. For this purpose, the SAS process can also be applied in order to co-precipitate molecules of interest with biocompatible and/or biodegradable polymers. An experimental study dealing with supercritical anti-solvent (SAS) precipitation has been carried out in order to micronize a biocompatible polymer, ethyl cellulose, widely used as a drug carrier in controlled delivery systems for oral administration. Supercritical carbon dioxide was used as anti-solvent for the polymer and ethyl acetate (EtAc), generally recognized as safe (GRAS) by the FDA (Food and Drug Administration) as solvent. The influence of the variation of the main operating parameters upon the characteristics of the micronized polymer was evaluated. In particular, the temperature (308, 318 and 333 K), the polymer concentration (1, 3 and 4 wt%), the EtAc/CO2 molar ratio (5 and 8 mol%) and the capillary tube diameter (127 and 254 μm) while pressure was kept constant and equal to 10 MPa. Using a low organic solution concentration of 1 wt% and at a temperature of 308 K, ethyl cellulose was successfully micronized in submicron particles with a mean size of 300 nm. However, increasing the temperature or the polymer concentration in the organic solution favored the particle coalescence and even led to fiber formation.
Rania Djerafi, Yasmine Masmoudi, Christelle Crampon, Abdeslam-Hassen Meniai, Elisabeth Badens. Supercritical anti-solvent precipitation of ethyl cellulose. Journal of Supercritical Fluids, Elsevier, 2015, 105, pp.92-98. 〈hal-01266175〉
Yasmine Masmoudi, Louiza Ben Azzouk, Olivier Forzano, Jean-Marie Andre, Elisabeth Badens. Supercritical impregnation of intraocular lenses. Journal of Supercritical Fluids, Elsevier, 2011, Selected Papers from the 9th Conference on Supercritical Fluids and their Applications, September 05-08, 2010, Sorrento (Italy), 60, pp.98 - 105. 〈hal-01266171〉 Plus de détails...
Supercritical impregnation can be used for the elaboration of controlled release systems that may be applied to pharmaceutical and medicinal fields. The present work is dedicated to the impregnation of intraocular lenses (IOLs) with antibiotics using supercritical carbon dioxide as impregnation vector. Commercially available intraocular lenses have been impregnated with cefuroxime sodium in order to obtain ophthalmic drug delivery systems dedicated to the prevention of postoperative endophthalmitis in cataract surgery. The influence of the variation of some experimental operating conditions such as the pressure (8–20 MPa), the temperature (308 and 333 K), the impregnation duration (1–5 h), the addition of a cosolvent (ethanol) or the depressurisation rate (slow and rapid depressurisation) has been studied. In certain experimental conditions, foaming phenomena have been observed. In order to evaluate the impregnation efficiency, the impregnation yields were quantified gravimetrically and the drug release profiles were determined through in vitro drug release studies carried out at 310 K and in a solution simulating the aqueous humor. At rapid depressurisation rates, controlled drug release IOLs with impregnation yields varying between 0.002 and 0.063 mgdrug/mgIOL were obtained. Increasing the pressure or adding a cosolvent were favourable to enhance the impregnation yields. However, a non desired foaming phenomenon was observed for the most favourable conditions. By carrying out slow depressurisations, foaming phenomena were avoided. Nevertheless, in these conditions, the impregnation process was less efficient. The drug partition seems to be more favourable towards the supercritical phase than towards the polymer and the impregnation phenomena governed by a deposition mechanism rather than a molecular dispersion of the active ingredient. The drug is almost deposited within the porosity created during the rapid depressurisation phase. This result was confirmed by the results of the drug release studies.
Yasmine Masmoudi, Louiza Ben Azzouk, Olivier Forzano, Jean-Marie Andre, Elisabeth Badens. Supercritical impregnation of intraocular lenses. Journal of Supercritical Fluids, Elsevier, 2011, Selected Papers from the 9th Conference on Supercritical Fluids and their Applications, September 05-08, 2010, Sorrento (Italy), 60, pp.98 - 105. 〈hal-01266171〉
Ruth-Astrid Strøm, Yasmine Masmoudi, Arnaud Rigacci, Georg. Petermann, Leif Gullberg, et al.. Strengthening and aging of wet silica gels for up-scaling of aerogel preparation. Journal of Sol-Gel Science and Technology, Springer Verlag, 2007, 41 (3), pp.291-298. 〈10.1007/s10971-006-1505-7〉. 〈hal-01266151〉 Plus de détails...
In order to enhance the mechanical properties of wet gels for aerogel production, aging studies by using three different routes was performed. The wet gels were prepared from a polyethoxydisiloxane precursor by using HF as a catalyst. The three different aging routes studied were i) aging in sealed mould, ii) aging in solvent and iii) aging in simulated pore liquid, i.e. a solvent with small amounts of water and HF resembling the mother liquor. All aging processes gave stronger and stiffer wet gels however, a maximum in strength and stiffness was observed after a certain aging time. The simulated pore liquids allowed short aging time in the range of 8 h to achieve the maximum mechanical strength, however the maximum in strength was lower than for the other two aging routes. From the wet gels, monolithic and transparent aerogels were obtained by supercritical drying at small-, mid- and large-scale. The aging strengthening process was successfully transferred to larger scales giving both lower density and higher transparency compared to small-scale.
Ruth-Astrid Strøm, Yasmine Masmoudi, Arnaud Rigacci, Georg. Petermann, Leif Gullberg, et al.. Strengthening and aging of wet silica gels for up-scaling of aerogel preparation. Journal of Sol-Gel Science and Technology, Springer Verlag, 2007, 41 (3), pp.291-298. 〈10.1007/s10971-006-1505-7〉. 〈hal-01266151〉
Journal: Journal of Sol-Gel Science and Technology
Yasmine Masmoudi, Arnaud Rigacci, Pierre Ilbizian, François Cauneau, Patrick Achard. Diffusion During the Supercritical Drying of Silica Gels. Drying Technology: An International Journal, 2006, 24 (9), pp.1121-1125. 〈10.1080/07373930600778270〉. 〈hal-01266137〉 Plus de détails...
Drying is the most critical elaboration step of large monolithic and crack-free silica aerogel plates. In the present work, we are studying the supercritical CO2 drying and more precisely the first step, here called the supercritical washing step. This phase consists of replacing the liquid phase contained in the nanopores with supercritical CO2. Within this study, this step is governed by molecular diffusion through the gels. These phenomena were investigated experimentally in order to estimate the duration of the washing step. The experimental results were then fitted with an analytical mass transfer model to identify the effective diffusion coefficient.
Yasmine Masmoudi, Arnaud Rigacci, Pierre Ilbizian, François Cauneau, Patrick Achard. Diffusion During the Supercritical Drying of Silica Gels. Drying Technology: An International Journal, 2006, 24 (9), pp.1121-1125. 〈10.1080/07373930600778270〉. 〈hal-01266137〉
Journal: Drying Technology: An International Journal